The objectives of this research proposal are to define some of the factors which regulate the synthesis of bile acids in health and disease. The diseases to be studied are cirrhosis and type II hypercholesterolemia. These objectives will include: 1. To determine if the normal pathway for bile acid synthesis takes place via 7 alpha-hydroxycholesterol. 2. To determine if the entire production of cholic and chenodeoxycholic acid takes place via 7 alpha-hydroxycholesterol in cirrhosis and hypercholesterolemia. 3. To measure the enzymatic activities of 7 alpha-hydroxylase, 12 alpha-hydroxylase and 5 beta-reductase in these two disease states. 4. To investigate the metabolism of bile acid intermediates in patients with neonatal cholestasis and childhood cirrhosis. Methods employed in these studies have been standardized in this laboratory and include the use of radiolabeled and mass-labeled compounds in patients with t-tube bile fistulas and patients with an intact enterohepatic circulation, synthesis of precursors, chromatography on celite, alumina, thin layer, and gas liquid systems, identification techniques such as I-R, UV, mass and NMR spectroscopy, and optical rotation method.